OXTR polymorphism predicts social relationships through its effects on social temperament

Humans have a fundamental need for strong interpersonal bonds, yet individuals differ appreciably in their degree of social integration. That these differences are also substantially heritable has spurred interest in biological mechanisms underlying the quality and quantity of individuals’ social relationships. We propose that polymorphic variation in the oxytocin receptor gene (OXTR) associates with complex social behaviors and social network composition through intermediate effects on negative affectivity and the psychological processing of socially relevant information. We tested a hypothesized social cascade from the molecular level (OXTR variation) to the social environment, through negative affectivity and inhibited sociality, in a sample of 1295 men and women of European American (N = 1081) and African American (N = 214) ancestry. Compared to European Americans having any T allele of rs1042778, individuals homozygous for the alternate G allele reported significantly lower levels of negative affectivity and inhibited sociality, which in turn predicted significantly higher levels of social support and a larger/more diverse social network. Moreover, the effect of rs1042778 variation on social support was fully accounted for by associated differences in negative affectivity and inhibited sociality. Results replicated in the African American sample. Findings suggest that OXTR variation modulates levels of social support via proximal impacts on individual temperament.     

Rabies virus nucleoprotein as a carrier for foreign antigens

Rabies virus (RV) nucleoprotein (N) tightly encapsidates the genomic and antigenomic RNA of RV to form the viral ribonucleoprotein (RNP) complex. Antigens, such as N, presented in a highly organized structure are sufficient and even desirable to activate B cells to proliferate and produce antibodies. In addition to activating B cells to proliferate, it has been shown that RV N in the RNP complex induces potent T helper cell responses resulting in long-lasting and strong humoral immune responses against RV. The possibility to systematically incorporate foreign genes into the genome of RV and produce a recombinant virus allows us to examine whether the immunogenicity of foreign antigens can be enhanced by incorporation into the RV RNP structure. To test this hypothesis we constructed a recombinant RV expressing a RV N-GFP fusion protein. The chimeric N-GFP fusion protein was efficiently expressed and incorporated into RV RNP and virions. Moreover, the recombinant RNP induces a strong humoral immune response against GFP in mice. In contrast, mice inoculated with GFP alone or a combination of wild-type RV RNPs and GFP did not trigger any GFP-specific humoral responses using the same immunization schedule. These data indicate the usefulness of RV-based vectors as killed vaccines against other infectious diseases.     

Non-steroidal anti-inflammatory drugs inhibit the processes of mucosal cell proliferation associated with duodenal ulcer healing.

We demonstrate that, in patients taking non-steroidal anti-inflammatory drugs (NSAIDs), there is inhibition of the proliferation of mucosal cells that normally leads to healing of duodenal ulcers. A microdissection technique was used to quantitate mitosis in duodenal crypts at the ulcer edge, giving a regeneration index of mitotic rate at that site, as compared to nearby mucosa. In patients with duodenal ulcers occurring in the absence of NSAID therapy, there was a brisk regenerative response (median index 2.48, range 1.55-9.81, n = 8), significantly greater than in patients taking NSAIDs (median index 1.10, range 0.73-2.16, n = 10, p = 0.014). Inhibition of the process of epithelial cell division normally involved in duodenal ulcer healing could contribute to the delay in ulcer healing which may explain the higher complication rate for duodenal ulcer during NSAID therapy.     

Overall accuracy of the BpTRU--an automated electronic blood pressure device

BACKGROUND: The objective of this report is to combine the data from an earlier adult study with the data from a paediatric study in order to determine the overall accuracy of the BpTRU (BPM-100 model) as compared to the recognized standard, auscultatory mercury sphygmomanometer. DESIGN: The individual blood pressure points recorded for both adult and paediatric studies were compared directly to its corresponding observer reference measurements from data collected and stored from the two separate studies. There were 255 sets of readings in the adult study and 162 sets from the paediatric study, which were combined to make 417 pairs of blood pressure readings for this study. METHODS: The overall observer standard reference mean for the 417 measurements was calculated and the difference between this and the overall mean BPM-100 was calculated with SD and ranges. Measurements within 5, 10 and 15 mmHg agreement were expressed as percentages. RESULTS: A total of 121 subjects were included for this study (85 from the adult study and 36 from the paediatric study). From these, 417 paired measurements were recorded. The mean difference between the BpTRU and the reference standard systolic blood pressure (BP) was 0.47+/-5.40 mmHg with 89.2% measurements within 5 mmHg, 96.4% within 10 mmHg and 99.3% within 15 mmHg. The mean difference between the BpTRU and reference diastolic BP was -2.12+/-5.93 mmHg with 81.1% within 5 mmHg, 92.1% within 10 mmHg and 97.6% within 15 mmHg. CONCLUSION: The BpTRU has been shown to be an accurate non-invasive blood pressure monitoring device in the general population over a wide range of ages (3-83 years). This combined study meets all requirements of the Association of Advancement of Medical Instrumentation and achieved a grade 'A' in the BHS protocol.     

Epoetin alfa improves quality of life in anemic HCV-infected patients receiving combination therapy

Anemia and decreased health-related quality of life (HRQL) are common in patients receiving combination therapy of interferon alfa (IFN) and ribavirin (RBV) for chronic hepatitis C virus (HCV) infection. In a randomized, prospective study evaluating the effectiveness of epoetin alfa in maintaining RBV dose, alleviating anemia, and improving HRQL in anemic (Hb < or = 12 g/dL) HCV-infected patients receiving combination therapy, patients receiving epoetin alfa had significant improvements in HRQL compared with placebo. In this study, 185 patients were randomized to 40,000 units of epoetin alfa subcutaneously weekly or placebo for an 8-week double-blind phase (DBP), followed by an 8-week open-label phase during which all patients received epoetin alfa. To further assess the impact of epoetin alfa on HRQL, post hoc analyses were conducted in the same patient population to compare the HRQL of these patients at randomization with norms of other populations, and to determine the critical relationship between hemoglobin (Hb) levels and HRQL. Mean HRQL scores of anemic HCV-infected patients receiving combination therapy at randomization were significantly lower than those of both the general population and patients who had other chronic conditions. Patients receiving epoetin alfa who had the greatest Hb increases from randomization to the end of the DBP also had the largest improvements in HRQL. Hb improvement was an independent predictor of HRQL improvement in these patients. In conclusion, epoetin alfa provided clinically significant HRQL improvement in HCV-infected patients receiving IFN/RBV therapy.     

Pathophysiologic correlations in asbestos-induced airway disease in the guinea pig

To determine whether asbestos-induced changes in the structure of the walls of small airways might be associated with abnormalities of pulmonary function, guinea pigs were given 10 mg of amosite asbestos (test group) or saline (control group) by intratracheal instillation. Pulmonary function tests performed 6 months later revealed significant increases in FRC, RV, and TLC in the test group. Measurement of airway wall thickness showed that both membranous and respiratory bronchioles were significantly thickened in the test group; this group also had airways of smaller internal diameter than the controls. Analysis for lung collagen content as hydroxyproline showed a 50% increase in the asbestos exposed animals. There was, however, only minimal and very focal interstitial fibrosis (asbestosis) in the lung parenchyma. Analysis of fiber size indicated that the fibers obtained by digestion of the tissue or from the lavage fluid were significantly longer and wider than those in the original asbestos sample; however, the tissue contained considerably larger fibers than the lavage fluid. We conclude that: Asbestos can produce airway fibrosis and narrowing causing air trapping on pulmonary function examination; this process occurs in the absence of significant interstitial fibrosis of the parenchyma (asbestosis), implying that abnormalities of pulmonary function which are consistent with airflow obstruction in asbestos exposed animals can be caused by pathologic changes in the small airways alone; long asbestos fibers are preferentially retained in the lung, and the longest fibers appear to be in a compartment inaccessible to lavage, presumably, in this model, in airway walls. Enhanced penetration of long fibers into tissue may be one reason why long fibers are more pathogenic than short ones.     

Value of the bipolar lead CM5 in electrocardiography.

Only bipolar lead recording are available during ambulatory monitoring. Their sensitivity in detecting ST segment changes in relation to standard electrocardiographic leads is not known. The magnitude and direction of ST segment changes in the bipolar lead CM5 were compared with those in standard electrocardiographic leads in patients during exercise testing and percutaneous transluminal coronary angioplasty. Thirty patients with coronary artery disease were studied during exercise tests in which ST segment depression (greater than 0.5 mm) occurred in one or more standard electrocardiographic leads and 13 patients were studied during angioplasty that resulted in ST segment change in one or more leads (I, II, III, V2, V5, and CM5). Lead CM5 was the most sensitive lead (93%) during exercise testing and also showed the greatest magnitude of ST segment change below the isoelectric line in 93% of the patients. Only two patients, one with ST segment elevation in inferior leads and one with changes restricted to septal leads, had no ST segment depression in lead CM5. When ST segment shift from the baseline electrocardiogram was measured the magnitude of depression was greatest in lead CM5 in only 63% of the patients. During angioplasty of the left anterior descending coronary artery, lead CM5 showed ST segment depression in seven patients, ST segment elevation in two, and a biphasic response in one. Two of the three patients with balloon inflation in right coronary artery developed ST segment elevation in lead CM5. Thus lead CM5 is a reliable lead for detecting subendocardial ischaemia experienced during everyday activities in anginal patients. During total occlusion of coronary arteries (as in variant angina or myocardial infarction) lead CM5 commonly shows ST segment depression and changes due to right coronary artery occlusion may not be detected.